“Call me Ishmael”
To say that I have read “Moby Dick” is a bit farcical. I was assigned the reading in high school and read enough to grasp the basic plot, a few key themes, and the ability to fake my way through class discussions by asserting that there is no correct or incorrect interpretation because Melville himself asserts that your version of the meaning is coloured by your life experiences. Therefore, “Moby Dick” could mean anything you want it to.
What on earth does this leviathan tale have to do with neurotech? Well, nothing. Not yet. Not until you see it through my life experiences.
Many years ago, while I was working with a close friend and colleague to populate the editorial board of a new journal, we made a dream list of candidates. The list was long and replete with what we then believed were the neurotech gods. We were successful in recruiting nearly everyone on our hunting list and had, over time, been able to meet and engage with our vast team of heavy hitters. One however, had always seemed to always just miss an in-person meeting. Travel schedules misaligned, conference sessions overlapped with other obligations, emergencies at home called us back early - we were repeatedly foiled. Thomas Stieglitz was our very own white whale.
After a lengthy series of near misses to meet in person, I finally met Dr. Stieglitz at NER in Shanghai in 2017 (in a poetic twist of fate, I’m working with Stieglitz on NER 2021 - stay tuned for more on that.) We had had exchanges about the journal but had never met face to face. The chase had elevated Stieglitz to mythical proportions. By the time we finally did meet, I was intimidated. I was nervous. I was jet lagged. I’m sure that my limited contribution to the larger lunch group that day was far from impressive. But unlike Ahab, I caught my white whale.
Curiously, literature continues to be a theme with Stieglitz. It was a book, one that still sits on his shelf as a reminder and inspiration, that brought him into neurotech. “Die Evolution entlässt den Geist des Menschen,” which translated loosely means “Evolution Releases the Mind (or spirit) of Man” was an accessible introduction to neurobionics and its goal of replacing damaged parts of the brain or spine with implanted devices. As a recent graduate of electrical engineering with an interest in physiology, this concept struck a chord with young Stieglitz. “I love electricity and I want to become an engineer and have a job where you can earn some money and do something that you understand halfway,” he recounted. “I immediately discovered that it could be really cool to combine electrical current and voltage and the human body with action potentials. That was in the end 80’s - early 90’s, so they thought that I’m completely crazy.”
Stieglitz performed his civil service in Germany as a paramedic where he discovered that, despite his love of the field of medicine, his bedside manner made him a less than ideal candidate for a physician. “I discovered that I don’t like all of that psychological talking to the persons to keep them calm,” he said. “I decided, well, probably you will never become a good doctor when you don’t like to talk.” Fortunately for the field of neurotechnology, no one had pointed out that he could have been an anaesthesiologist or a pathologist. “Right. If you have a tube in their throat or they don’t talk anymore, that could have worked. That was one of those decisions that you make for really naive reasons, and that was my reason not to study medicine,” continued Stieglitz. Or, as Ishmael would say, “I try all things, I achieve what I can.”
Walk with me for a moment down a little side street. Please, indulge me. I cannot stand the necessary but trite phrases of these past months - the obsequious, but mandatory opening to any commercial, entreaty, newscast, or explanation. Can we rid ourselves of the cringe worthy “In these unusual times...” or “troubled” or “unparalleled” or “unprecedented”? Agreed? Good. Thank you. So, banal (un)pleasantries aside, we cannot ignore the effect of COVID-19 on research. I can’t imagine how everyone is managing to advance their research with lab closures, changes in resources, and the draw to use your talents and apply them to the “current crisis.” With experiments on hold indefinitely, I suppose it’s something akin to making do with what you have in the pantry. If that’s the case, Stieglitz might just be a doomsday prepper.
While Freiburg has been under stay at home orders, Stieglitz has used the time to analyze data, clear up the queue of administrative work, writing grant reports, drafting grant proposals, refining papers, and counseling students. He admits that the work goes slower these days, but that video conferencing is sufficient to get through everything. As his lab at the University of Freiburg re-opens, the new normal (another unctuous term I hope will die soon) will include a shift-based system with only two or three persons in the lab at a time. Clean room work can also resume. Given the requisite masks, gloves, coats, and caps, clean rooms perhaps have been the safest places to be over the last few months; nothing there will change.
“It probably helps that people can use this time to better design studies,” suggested Stieglitz. “If you’re now sitting at home and you cannot work that much, I hope that people don’t use an even thinner data basis. I hope we are thinking more about solid work that will get published; it will be better to have one really sound and solid paper than two that are not that sound.”
Even with every effort to be productive during quarantine, it’s not hard to see that there will be a ripple effect in publications. The interruption to animal work will create a dearth of data. Perhaps this is the time to more strongly consider opportunities to share data. Or not. When I asked Stieglitz his thoughts, he pointed out what should have been obvious, but that I had failed to fully think through. “I would imagine that people are afraid that money now will go in different channels and no longer in the same amounts for this kind of research,” he explained. “A lot of money is now funneled into COVID-19 research so there will probably be a reallocation of budgets with respect to neural engineering. If data is your currency to publish, why share it?”
Stieglitz, as a member of multiple editorial boards and a recipient of J. Neuroscience Methods’ “Top Reviewer Award,” is clearly qualified to offer an opinion on the quality of data. “The recent papers I had to review or send out for review were not of that quality that I would have expected if you have access to so many data,” he laments. “If you can save the time for data acquisition, you should take the time to design your study on rock solid data analysis. I don’t see a strong correlation between having [a lot of] data and having really high-level publications. And! Sharing data would be good if you would have high quality annotated data.”
There are probably as many ways of presenting data sets as there are groups acquiring the data. Different groups have difficulty agreeing on uniform collection formats regardless of the discipline. With such differences, annotation becomes the saving grace. Stieglitz says that we have a long way to go and points out the necessity to create some sort of trusteeship to assume responsibility and care for the data and to implement data protection to ward off violation. That brokerage service must be provided by a trustworthy entity with the resources to endure for the life of the need for that data. That data would also have to include scrupulous annotation.
But I digress. We were talking about the effects of COVID-19 on neural engineering research (aren’t we always talking about COVID-19 these days?) We circled back to the topic and landed on the funding implications. “It’s just a feeling,” opined Stieglitz. “But the amount of money is always limited. Always. Now, where you have no option for personal lobbying at conferences or meetings, how to do the lobbying? At conferences we could meet with an officer and share some fantastic big thoughts.”
In these (stupid, lame, infuriating, frustrating, scary,) times, our lack of personal contact can hinder our professional progress. Stieglitz was within a fortnight (no, not “Fortnite,” the game) of the Gordon Research Conference on Neuroelectronic Interfaces, when he and his co-chair, T.K. Kozai and vice chairs, Jack Judy and Stéphanie Lacour made the difficult decision to postpone. They were the first conference casualty in our community. 2020 would have been the second iteration of this conference and promised to be outstanding. The conference will proceed... in 2022. I asked Stieglitz about the impact of cancelling and the disappointment at watching so much effort be seemingly wasted. He gave a good-natured chuckle.
“I think we have a really outstanding program. Now it’s postponed for two years. I think we’ll have to adapt the topics, but I’m pretty sure that the topics that we have chosen will still be relevant two years from now,” he said. “I would be glad to see that everything would be solved by then - that would be awesome because then we would have some pretty cool devices serving patients’ needs, but I don’t think we’ll be there yet. I think we will still be cool enough in two years. Perhaps we will make a special issue or two. We want to keep spirits high over the next two years.”
As for the personal losses that Stieglitz feels during quarantine, it seems to be the simple things that many of us now realize we may have taken for granted. Workwise, we almost see more of our colleagues with the near-fanatic use of Zoom (of which I am guilty; this interview was conducted via Zoom.) It is the spontaneous interactions and anonymous observations that are missing. “You can have email exchanges and video calls, but you don’t have that contact over a cup of coffee or just seeing somebody sitting in the lab to say ‘Hey, that looks exciting.’ Personally, we have enough space at home, we have a garden, the weather is fine. There’s nothing to complain about, but I like sitting in a cafe, just watching persons go by and watching - the little things. I’d say that’s really life.”
I was fortunate enough to have a coffee (ok, we all know it was really a beer) at a cafe near Stieglitz’s office last spring. He is right. That really is life. “JoJo, what were you doing all the way in Freiburg?” you ask. Well, I was lucky enough to attend a conference put on by one of Stieglitz’s brainchild companies, CorTec.
CorTec is delivering electrodes for small nerve diameters for bioelectronic medicine research. “I’m always very proud to see that they are currently the standard against which young PhD students develop new electrodes,” waxed Stieglitz. “I mean, this is something if you come to be the standard that others say, ‘Well, this is the state of the art.’ This is really nice to see after only a few years that they really made it to that point.”
Stieglitz quickly pointed out that these electrodes are predominantly used for relatively fundamental research before sharing their latest developments. CorTec has raised the bar for the quality of electrodes used in basic research. They are manufactured under rigorous manufacturing standards and deliver high signal quality and longevity. Their cortical electrode array has received a 510k approval for the US. Human applications are the first piece of the path. The wireless system with a bidirectional implant for recording brain activity, for stimulating, and for doing closed-loop control is on the way towards human applications, hopefully in the next 18 months or so.
Stieglitz’s second start up, neuroloop, is developing a platform technology for selective vagal nerve stimulation. The (pre-COVID-19) business plan targeted in-human studies in the “near future”. After five or six human patients as part of the first cohort, the next step is approval studies for the European CE mark to treat hypertension. Although they typically do not comment on on-going research, I was able to get Dr. Michael Lauk, neuroloop’s CEO and co-founder, to offer a small glimpse of their progress. “We are currently on our path to first-in-human, which is planned for later this year,” he said. “Our pre-clinical results are very encouraging, so stay tuned, we will start publishing more details hopefully in 2021.”
I asked Stieglitz what his plans for might be a third start up. “I think that two is probably enough. I have no brilliant idea for a third and a fourth one; let’s see what comes next,” he said and immediately contradicted himself with excitement about his group’s sensory feedback work.
Stieglitz is currently working on two lines that meet in the middle to form a bigger picture concept. The goal is to have bidirectional neural interfaces that are stable in the long term and designed with a better understating of what makes them fail in order to design appropriate counter measures. He confesses that the system failure analysis “doesn’t sound that spectacular for a business,” but also pointed out that the tedium of understanding the cellular responses, material deterioration, and the chemistry is important work for his own designs and for the field at large. Understanding the body’s interaction with the devices themselves as well as potential signal interference is as important as finding the balance between the current load and the foreign body response. Where is the balance between optimal signal strength and tissue preservation? Where can improvements be made?
His second line of the same drawing is how to talk to the nervous system and how to stimulate in a way that takes into account the whole person, not just the missing or broken part. Stieglitz walked me through some of the recent research being done in sports medicine and movement sciences. He underscored the need to understand the influences on gait between how persons with artificial legs walk versus how those with one or no prosthetics walk. Are there inherent differences that should be considered? Prosthetics can’t use our natural neural signals because the mechanics are different. “I talked to a friend of mine and said, ‘Of course you need a co-contraction of all muscles with a leg prosthesis - and swing force.’ That’s stupid and easy once you have heard it, but if you do rehabilitation, and you look from a different side saying ‘Oh, I want to have exactly the same activation pattern in the brain,’ probably that is nonsense,” he explained.
Work in the Stieglitz lab incorporates input from neurotech, movement scientists, artificial intelligence, and robotics. He is focused on inclusive conversations to benefit from the knowledge of others and to make something that is more reliable and more intuitive. He strives to address such questions as how to examine things as they interact within the bigger frame work, how much support needs to be included, what are you able to do and how do you get there, can the robotics learn these things intuitively and what are the good or important markers to reliably communicate throughout the system and to the user? What are the questions we haven’t even asked yet? He gave the example of the role of trunk and hip muscles and their signals to the brain if there is no sensory feedback. In a healthy system sensory feedback tells the system where the foot is, what type of terrain is present. In a prosthetic system we need to better understand what feedback is necessary and then we need to determine how to deliver the best coding to the mechanism and can we somehow optimize or trick out the system a little bit. Once that is done, we need to develop the electrodes that can exactly deliver what is needed.
I asked him about the sensory feedback papers that had recently been published by Battelle and others. “I think that’s only one piece,” said Stieglitz. “Silvestro’s group and Raspopovic's, these publications last year on upper knee amputees and the sensory feedback - that outcome was really overwhelming, but I think it’s a starting point. It’s not the final truth. We have to learn more what they really need in daily life and deliver on that.” This is an idea his colleagues fully embrace.
“This work and stunning results with BCIs impressively demonstrate the importance of closed-loop control but also shows large potential for further developments,” commented CorTec’s CEO, Martin Schuettler, Ph.D. “In particular, patients will benefit from completely implanted technology that does not require complicated lab equipment to operate, hence does not restrict the patient’s mobility and also does not require daily do-on / do-off and calibration procedures. It is precisely this potential that CorTec’s Brain Interchange System should exploit in the future as a closed-loop system, applicable to many other applications.”
Stieglitz understands the necessity of publishing and is quite prolific in that area, but his bottom line is really trying to make a positive impact in a user’s daily life. Cool engineering is really only cool if it helps people. “Typical fundamental research is that every two, three years you have to get a brilliant idea and then you get one paper. That’s not my driving force. I want to really stick with a few ideas and work on them for 10 years or longer and see that they evolve into something useful.
“I love to work on something where I have the feeling that I could really help somebody on the very long term. I really want to see one of my ideas on that very, very long-term run being in patients and in a product.”
Now it appears that Stieglitz is the one hunting the white whale. His career quest is to deliver meaningful, stable devices and to make an impact on users. Like me, and unlike Ahab, I know that he will land his prize.